Optically active diphosphines, preparation thereof according to a process for the resolution of the racemic mixture and use thereof

ABSTRACT

New optically active bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] diphosphines and new optically active transition metal complexes with said phosphines are described. The complexes are useful as catalysts to promote hydrogenation of substrates.

This application is a divisional of application Ser. No. 09/498,466,filed on Feb. 4, 2000, which is a divisional of application Ser. No.09/025,441, filed Feb. 17, 1998 now U.S. Pat. No. 6,037,493, which is adivisional of application Ser. No. 08/696,824, filed Oct. 4, 1996 nowU.S. Pat. No. 5,783,738, which is a §371 of PCT Application No.PCT/FR95/01716, filed Dec. 22, 1995.

The present invention relates to optically active diphosphines. It isalso targeted at their preparation according to a process for theresolution of the racemic mixture of the said phosphines to opticallyactive isomers.

More precisely, the subject of the invention is new optically activebis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] diphosphines andthe process for the resolution of the racemicbis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] mixture.

The invention also relates to new optically active metal complexescomprising the said phosphines and to their use in a process for thepreparation of optically active carboxylic acids and/or derivativesaccording to a process for the hydrogenation of α,β-unsaturatedcarboxylic acids and/or derivatives.

The preparation of a mixture ofbis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] diastereoisomershas been described by F. Mathey et al. in Bull. Soc. Chim. Fr., 129, pp.1-8 (1992).

The starting material in the synthesis of the latter is1-phenyl-3,4-dimethylphosphole (II) described by F. Mathey et al. inSynthesis, 1983, pp. 983.

The starting point is the preparation of3,3′,4,4′-tetramethyl-1,1′-diphosphole (IV). To this end,1-phenyl-3,4-dimethylphosphole (II) is reacted in THF with lithium metalaccording to the following reaction:

At the end of the reaction, aluminium chloride is introduced in order totrap the phenyllithium produced during the reaction.

In a following stage, (III) is dimerized by the action of diiodine I₂ inTHF. For more details on the preparation of (IV), reference may be madeto the article by F. Mathey et al., Organometallics, 1983, 2, 1234.

On heating to approximately 140° C., the compound (IV) rearranges to(V), which reacts with diphenylacetylene according to the Diels-Alderreaction, to give bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene].

A practical embodiment is given on page 6 of the publication by F.Mathey et al. in Bull. Soc. Chim. Fr., 129, pp. 1-8 (1992).

However, the writers obtained, as mentioned on page 3, right-handcolumn, lines 7 and 8, a mixture of two diastereoisomers subsequentlyidentified by the Applicant Company as being a meso (I m)—RS,SR—and aracemate (I r)—RR,SS—called (13b) and (13a) respectively in the article.

The publication mentions the separation of the two diastereoisomers byformation of a palladium(II) chelate. To do this, a description is givenof the separation of the mixture of diastereoisomers obtained byreaction with PdCl₂(PhCN)₂ in dichloroethane, resulting in (VI m) and(VI r), and the separation by chromatography on silica gel, followed byelution and then by a decomplexation carried out by NaCN.

The two diastereoisomers, on the one hand the meso (I m) and, on theother hand, the racemate (I r), are thus recovered separately.

The document of the state of the art does not describe the separation ofthe enantiomers.

The problem of resolving two enantiomers is difficult to solve when thechirality is carried by the phosphorus.

An object of the present invention is to provide new, bidentate,optically active disphosphines which are chiral on the phosphorus andwhich cannot be racemized.

Another object of the present invention is to make available a processwhich makes it possible to obtain them according to a process forresolving the racemicbis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] mixture.

Finally, another object of the invention is to have available a processfor the preparation of optically active carboxylic acids and/orderivatives according to a process for the hydrogenation ofα,β-unsaturated carboxylic acids and derivatives which makes use ofmetal complexes using the optically active diphospine as ligand.

According to a first subject of the present invention, new opticallyactive bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene]diphosphines have been found which correspond to the following formulae:

According to another subject of the invention, the racemicbis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] mixture isresolved according to a process which comprises reacting it with apalladium and/or platinum complex as chiral auxiliary in an organicsolvent, thus forming diastereoisomer complexes, and then resolving thesaid optically pure complexes.

In accordance with the process of the invention, a palladium complex isused. This type of chiral auxiliary is widely described in theliterature, in particular by Sei Otsuka et al. in Journal of theAmerican Chemical Society, 93, pp. 4301 (1971).

A platinum complex can also be used and reference may more particularlybe made to the work by A. C. Cope [Journal of the American ChemicalSociety, 90, pp. 909 (1968)].

The chiral complex used more particularly corresponds to the generalformula (VII):

in the said formula:

M represents palladium and/or platinum,

R₁, R₂, R₃ and R₄ represent a hydrogen atom or an alkyl radical havingfrom 1 to 10 carbon atoms or a cycloalkyl radical having from 3 to 10carbon atoms,

R₃ and R₄ are different and at least one of the two represents ahydrogen atom,

R has the meaning given for R₁, R₂, R₃ and R₄,

X represents a halogen atom,

n is a number from 0 to 4,

when n is greater than 1, two R radicals and the 2 successive atoms ofthe benzene ring can form, between them, a ring having from 5 to 7carbon atoms.

More preferentially, the complex used corresponds to the abovementionedformula in which R₁, R₂, R₃ and R₄ represent a hydrogen atom or a methylradical, X represents a chlorine atome and n is equal to 0.

When n is equal to 2, two R radicals form a benzene ring.

Mention may be made, as more specific examples of palladium complexeswhich are suitable for the present invention, obtained withoutdistinction from (R)-(+)- or (S)-(−)-N,N-dimethylphenylethylamine, of:

The amount of complex of the abovementioned metals, expressed as metal,is generally from 0.5 to 1 metal atom per phosphorus atom.

An organic solvent is used which dissolves all the reactants. Thesolvent must be inert with respect to the diphosphine.

Mention may be made, as non-limiting examples of solvents which aresuitable in the process of the invention, of:

aliphatic hydrocarbons and more particularly paraffins such as, inparticular, pentane, hexane, heptane, octane, isooctane, nonane, decane,undecane, tetradecane, petroleum ether and cyclohexane; aromatichydrocarbons such as, in particular, benzene, toluene, xylenes,ethylbenzene, diethylbenzenes, trimethylbenzenes, cumene, pseudocumeneor petroleum fractions composed of a mixture of alkylbenzenes, inparticular fractions of Solvesso® type,

halogenated aliphatic or aromatic hydrocarbons, and mention may be madeof: perchlorinated hydrocarbons such as, in particular, trichloromethaneor tetrachloroethylene; partially chlorinated hydrocarbons, such asdichloromethane, dichloroethane, tetrachloroethane, trichloroethylene,1-chlorobutane or 1,2-dichlorobutane; or monochlorobenzene,1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene ormixtures of different chlorobenzenes.

Benzene and toluene are preferred among all these solvents.

The concentration of the diphosphine in the reaction solvent ispreferably between 0.05 and 1 mol/liter and more particularly stillbetween 0.05 and 0.2 mol/liter.

Separation is advantageously carried out at ambient temperature,generally between 15° C. and 25° C.

It preferably takes place under a controlled atmosphere of inert gases.A rare gas atmosphere, preferably of argon, can be set up but it is moreeconomical to use nitrogen.

A mixture of complexes of palladium or platinum and of diphosphinecorresponding to each enantiomer is obtained.

Another subject of the invention is the intermediate product, namely themetal complex with the diphosphines of formula:

in the said formulae M represents palladium or platinum, X a halogenatom, preferably chlorine, and A symbolizes the residue of a chiralmetal complex corresponding to one of the formulae (VII) andpreferentially (VII′).

The two pure enantiomers are recovered in a following stage.

The solvent is concentrated by evaporation and separation is thencarried out in a known way [A. Bertheillier-Dunod Paris (1972)] byliquid chromatography on a column with, preferably, a support made ofsilica.

The column is eluted with a mixture of suitable solvents, preferably atoluene/ethyl acetate mixture preferentially comprising 80% by volume oftoluene and 20% by volume of ethyl acetate.

The two pure isolated enantiomers are recovered in the form of twodiastereoisomer complexes having the following characteristics:

³¹P NMR=δ(CH₂Cl₂)=55.9 ppm

³¹P NMR=δ(CH₂Cl₂)=53.6 ppm

The two pure enantiomers of the diphosphine are recovered by carryingout decomplexation.

To this end, use is made in particular of a hydrocyanic acid salt,preferably an alkali metal salt and more preferentially still the sodiumsalt: the said salt being dissolved in the minimum amount of waternecessary.

The complexes are dissolved in an organic solvent such as, for example,dichloromethane and then the hydrocyanic acid salt, generally used in anexcess representing from 2 to 5 mol per metal atom, is introduced withstirring.

The operation is also carried out under a controlled atmosphere and atambient temperature.

The enantiomer is recovered in the organic phase, which phase isseparated, washed with water and dried, for example over sodiumsulphate.

The two pure isolated enantiomers ofbis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] corresponding tothe abovementioned formulae [(S,S)-(+)-(Ia)] and [(R,R)-(−)-(Ib)] areobtained, the characteristics of which are as follows:

³¹P NMR=δ(CDCl₃)=−13.2 ppm; [α]_(D)=+231° (c=1, C₆D₆).

³¹P NMR=δ(CDCl₃)=−13.2 ppm; [α]_(D)=−198° (c=1, C₆D₆)

(with an [α]_(D) determined for a concentration of 10 mg/ml and atambient temperature).

It has also been found, which constitutes another subject of the presentinvention, that the new optically active diphosphines as mentioned abovein the form of metal complexes could be used as catalysts for theasymmetric hydrogenation of α,β-unsaturated carboxylic acids and/orderivatives.

The optically active diphosphines of formula (Ia) or (Ib) are used asligands in the formation of complexes with transition metals.

A subject of the invention is therefore new complexes comprising anoptically active diphosphine and a transition metal which arecharacterized in that the ligand corresponds to one of the followingformulae:

Mention may be made, as examples of transition metals capable of formingcomplexes, of in particular metals such as rhodium, ruthenium, rhenium,iridium, cobalt, nickel, platinum or palladium.

Rhodium, ruthenium and iridium are preferred among the abovementionedmetals.

Specific examples of the said complexes of the present invention aregiven hereinbelow, without limiting nature.

In the said formulae, (P*P) represents the diphosphine of formula (Ia)or (Ib).

The rhodium and iridium complexes can be represented by the followingformulae:

[M L₂(P*P)]Y  (IIa)

[M L₂(P*P)]Y  (IIb)

in the said formulae:

(P*P) represents, in the formula (IIa), the diphosphine of formula (Ia)and, in the formula (IIb), the diphosphine of formula (Ib),

M represents rhodium or iridium,

Y represents an anionic coordinating ligand,

L represents a neutral ligand.

The preferred rhodium or iridium complexes correspond to the formula(IIa) or (IIb) in which:

L represents an olefin having from 2 to 12 carbon atoms and two Lligands can be joined to one another in order to form a linear or cyclicpolyunsaturated hydrocarbon chain; L preferably representing1,5-cyclooctadiene, norbornadiene or ethylene,

Y represents a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻, BPh₄ ⁻,ClO₄ ⁻, CN⁻ or CF₃SO₃ ⁻ anion, halogen, preferably Cl⁻ or Br⁻, a1,3-diketonate, alkylcarboxylate or haloalkylcarboxylate anion with alower alkyl radical, or a phenylcarboxylate or phenoxide anion in whichthe benzene ring can be substituted by lower alkyl radicals and/orhalogen atoms.

The term lower alkyl radicals is generally understood to mean a linearor branched alkyl radical having from 1 to 4 carbon atoms.

Other iridium complexes can be represented by the formulae:

[IrL(P*P)]Y  (IIIa)

[IrL(P*P)]Y  (IIIb)

in the said formulae (P*P), L and Y have the meanings given for theformulae (IIa) and (IIb).

As regards the ruthenium complexes, they preferentially correspond tothe following formulae:

[RuY₁Y₂(P*P)]  (IVa)

[RuY₁Y₂(P*P)]  (IVb)

in the said formulae:

(P*P) represents, in the formula (IVa), the diphosphine of formula (Ia)and, in the formula (IVb), the diphosphine of formula (Ib),

Y₁ and Y₂, which are identical or different, preferably represent a PF₆⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻, BPh₄ ⁻, ClO₄ ⁻ or CF₃SO₃ ⁻anion, a halogen atom, more particularly chlorine or bromine, or acarboxylate anion, preferentially acetate or trifluoroacetate.

Other ruthenium complexes capable of being used in the process of theinvention correspond to the formulae hereinbelow:

[RuY₁Ar(P*P)Y₂]  (IVc)

[RuY₁Ar(P*P)Y₂]  (IVd)

in the said formulae:

(P*P) represents, in the formula (IVc), the diphosphine of formula (Ia)and, in the formula (IVd), the diphosphine of formula (Ib),

Ar represents benzene, p-methylisopropylbenzene or hexamethylbenzene,

Y₁ represents a halogen atom, preferably chlorine or bromine,

Y₂ represents an anion, preferably a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆⁻, SbCl₆ ⁻, BPh₄ ⁻, ClO₄ ⁻ or CF₃SO₃ ⁻ anion.

It is also possible to use complexes based on palladium and on platinumin the process of the invention.

Mention may be made, as more specific examples of the said complexes,of, inter alia, PdCl₂(P*P) and PtCl₂(P*P) in which (P*P) represents thediphosphine of formula (Ia) or (Ib).

The complexes comprising the abovementioned diphosphine and thetransition metal can be prepared according to the known processesdescribed in the literature.

For the preparation of the ruthenium complexes, reference may inparticular be made to the publication by J.-P. Genêt [Acros OrganicsActa, 1, No. 1, pp. 1-8 (1994)] and, for the other complexes, to thearticle by Schrock R. and Osborn J. A. [Journal of the American ChemicalSociety, 93, pp. 2397 (1971)].

They can be prepared in particular by reaction of the diphosphine offormula (Ia) or (Ib) with the transition metal compound in a suitableorganic solvent.

The reaction is carried out at a temperature of between ambienttemperature (from 15 to 25° C.) and the reflux temperature of thereaction solvent.

Mention may be made, as examples of organic solvents, of, inter alia,halogenated or non-halogenated aliphatic hydrocarbons and moreparticularly hexane, heptane, isooctane, decane, benzene, toluene,methylene chloride or chloroform; solvents of ether or ketone type andin particular diethyl ether, tetrahydrofuran, acetone or methyl ethylketone; or solvents of alcohol type, preferably methanol or ethanol.

The metal complexes according to the invention, recovered according toconventional techniques (filtration or crystallization), are used inreactions for the asymmetric hydrogenation of substrates specifiedhereinbelow.

Another object of the present invention is to provide a process for thepreparation of an optically active carboxylic acid and/or derivative,which process is characterized in that an α,β-unsaturated carboxylicacid and/or its derivatives is/are asymmetrically hydrogenated in thepresence of an effective amount of a metal complex comprising, asligand, the optically active diphosphine of formula (Ia) or (Ib) and atransition metal.

The α,β-unsaturated carboxylic acid and/or its derivatives correspondsmore particularly to the formula (V):

in the said formula (V):

R₁, R₂, R₃ and R₄ represent a hydrogen atom or any hydrocarbon group,insofar as:

if R₁ is other than R₂ and other than a hydrogen atom, then R₃ can beany functional or hydrocarbon group denoted by R,

if R₁ or R₂ represents a hydrogen atom and if R₁ is other than R₂, thenR₃ is other than a hydrogen atom and other than —COOR₄,

if R₁ is identical to R₂ and represents any functional or hydrocarbongroup denoted by R, then R₃ is other than —CH—(R)₂ and other than—COOR₄,

it being possible for one of the R₁, R₂ and R₃ groups to represent afunctional group.

The R₁ to R₄ radicals, which are identical or different, represent anoptionally substituted hydrocarbon radical having from 1 to 20 carbonatoms which can be a linear or branched, saturated or unsaturated,acyclic aliphatic radical; a monocyclic or polycyclic, saturated,unsaturated or aromatic, heterocyclic or carbocyclic radical; or alinear or branched, saturated or unsaturated, aliphatic radical carryinga cyclic substituent.

In the general formula (V), R₁ to R₄, which are identical or different,can take various meanings. Different examples are given hereinbelow butthey are in no way limiting.

Thus, the R₁ to R₄ radicals preferentially represent an aromatichydrocarbon, and in particular benzene, radical corresponding to thegeneral formula (V′):

in the said formula (V′):

n is an integer from 0 to 5, preferably from 0 to 3;

Q represents R₀, one of the following groups or functional groups:

a linear or branched alkyl radical having from 1 to 6 carbon atoms,preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, sec-butyl or tert-butyl,

a linear or branched alkenyl radical having from 2 to 6 carbon atoms,preferably from 2 to 4 carbon atoms, such as vinyl or allyl,

a linear or branched alkoxy radical having from 1 to 6 carbon atoms,preferably from 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy,isopropoxy and butoxy radicals,

an acyl group having from 2 to 6 carbon atoms,

a radical of formula:

—R₅—OH

—R₅—COOR₇

—R₅—CHO

—R₅—NO₂

—R₅—CN

—R₅—N(R₇)₂

—R₅—CO—N(R₇)₂

—R₅—SH

—R₅—X

—R₅—CF₃

in the said formulae R₅ represents a valence bond or a saturated orunsaturated, linear or branched, divalent hydrocarbon radical havingfrom 1 to 6 carbon atoms such as, for example, methylene, ethylene,propylene, isopropylene or isopropylidene; R₇ represents a hydrogen atomor a linear or branched alkyl radical having from 1 to 6 carbon atoms;and X symbolizes a halogen atom, preferably a chlorine, bromine orfluorine atom.

Q represents R₀′, one of the following, more complex radicals:

 in which:

m is an integer from 0 to 5, preferably from 0 to 3,

R₀ has the meaning give above,

R₆ represents a valence bond; a saturated or unsaturated, linear orbranched, divalent hydrocarbon group having from 1 to 6 carbon atomssuch as, for example, methylene, ethylene, propylene, isopropylene orisopropylidene or one of the following groups known as Z:

—O—; —CO—; —COO—; —NR₇—; —CO—NR₇—; —S—; —SO₂— or —NR₇—CO—;

 in the said formulae R₇ represents a hydrogen atom or a linear orbranched alkyl group having from 1 to 6 carbon atoms, preferably amethyl or ethyl radical.

When n is greater than 1, the Q radicals can be identical or differentand 2 successive carbon atoms of the benzene ring can be joined to oneanother by a ketal bridge, such as the methylenedioxy or ethylenedioxyextranuclear radicals.

Preferably, n is equal to 0, 1, 2 or 3.

Among all the abovementioned R₁ to R₄ radicals, use is verypreferentially made, in the process of the invention, of carboxylicacids or derivatives corresponding to the general formula (V) in whichR₁ to R₄ represent an aromatic radical corresponding to the generalformula (V′) in which:

n is equal to 0, 1, 2 or 3,

Q represents one of the following groups or functional groups:

a hydrogen atom,

linear or branched alkyl radical having from 1 to 4 carbon atoms,

a linear or branched alkoxy radical having from 1 to 4 carbon atoms,

a benzoyl group,

an —OH group,

a —CHO group,

an NH₂ group,

an NO₂ group,

a phenyl radical,

a halogen atom,

a CF₃ group.

More preferentially still, the compounds of formula (V) are chosen inwhich the Q radicals, which are identical or different, are a hydrogenatom, an alkyl radical having from 1 to 4 carbon atoms, a methoxyradical, a benzoyl group or an NO₂ group.

Mention may more specifically be made, as examples of R₁ to R₄ radicalscorresponding to the formula (V), of phenyl, tolyl or xylyl,1-methoxyphenyl and 2-nitrophenyl radicals and biphenyl,1,1′-methylenebiphenyl, 1,1′-isopropylidenebiphenyl,1,1′-carboxybiphenyl, 1,1′-oxybiphenyl and 1,1′-iminobiphenyl radicals:it being possible for the said radicals to be substituted by one or anumber of Q radicals as defined above.

R₁ to R₄ can also represent a polycyclic aromatic hydrocarbon radical;it being possible for the rings to form, between themselves, ortho-fusedand ortho- and peri-fused systems. Mention may more particularly be madeof a naphthalene radical; it being possible for the said rings to besubstituted by 1 to 4 R₀ radicals, preferably 1 to 3 R₀ radicals, R₀having the meanings stated above for the substituents of the aromatichydrocarbon radical of general formula (V′).

In the general formula (V) of the carboxylic acids, R₁ to R₄ can alsorepresent a saturated carbocyclic radical or a carbocyclic radical whichcomprises 1 or 2 unsaturations in the ring and which generally has from3 to 7 carbon atoms, preferably 6 carbon atoms, in the ring; it beingpossible for the said ring to be substituted by 1 to 5, preferably 1 to3, R₀ radicals, R₀ having the meanings stated above for the substituentsof the aromatic hydrocarbon radical of general formula (V′).

Mention may be made, as preferred examples of R₁ to R₄ radicals, ofcyclohexyl or cyclohexenyl radicals, optionally substituted by linear orbranched alkyl radicals having from 1 to 4 carbon atoms.

As mentioned above, R₁ to R₄ can represent a linear or branched,saturated or unsaturated, acyclic aliphatic radical.

More precisely, R₁ to R₄ represent a linear or branched acyclicaliphatic radical preferably having from 1 to 12 carbon atoms which issaturated or which comprises one to a number of unsaturations in thechain, generally 1 to 3 unsaturations, which can be double bonds, whichare simple or conjugated, or triple bonds.

The hydrocarbon chain can optionally be:

interrupted by one of the following Z groups:

—O—; —CO—; —COO—; —NR₇—; —CO—NR₇—; —S—; —SO₂— or —NR₇—CO—;

 in the said formulae R₇ represents a hydrogen atom or a linear orbranched alkyl group having from 1 to 6 carbon atoms, preferably amethyl or ethyl radical,

and/or a carrier of one of the following substituents:

—OH, —COOR₇—CHO, —NO₂, —CN, —NH₂, —SH, —X or —CF₃.

 R₇ having, in these formulae, the meaning given above.

It is also possible to use a carboxylic acid or derivative of formula(V) in which R₁ to R₄ represent a linear or branched, saturated orunsaturated, acyclic aliphatic radical which can optionally carry acyclic substituent. Ring is understood to mean a saturated, unsaturatedor aromatic heterocyclic or carbocyclic ring.

The acyclic aliphatic radical can be joined to the ring by a valencebond or by one of the abovementioned Z groups.

It is possible to envisage, as examples of cyclic substituents,cycloaliphatic, aromatic or heterocyclic substituents, in particularcycloaliphatic substituents comprising 6 carbon atoms in the ring orbenzene substituents, these cyclic substituents being themselvesoptionally the carriers of 1, 2, 3, 4 or 5 identical or different R₀radicals, R₀ having the meanings stated above for the substituents ofthe aromatic hydrocarbon radical of general formula (V′).

Mention may be made, as examples of such radicals, of, inter alia, thebenzyl radical.

In the general formula (V) of the carboxylic acids, R₁ to R₄ can alsorepresent a saturated or unsaturated heterocyclic radical containing inparticular 5 or 6 atoms in the ring, including 1 or 2 heteroatoms, suchas nitrogen, sulphur and oxygen atoms; it being possible for the carbonatoms of the heterocycle optionally to be substituted, in their entiretyor for only a portion of them, by R₀ radicals, R₀ having the meaningsstated above for the substituents of the aromatic hydrocarbon radical ofgeneral formula (V′).

R₁ to R₄ can also represent a polycyclic heterocyclic radical defined asbeing either a radical composed of at least 2 aromatic or non-aromaticheterocycles containing at least one heteroatom in each ring and formingbetween them ortho- or ortho- and peri-fused systems or either a radicalcomposed of at least one aromatic or non-aromatic hydrocarbon ring andat least one aromatic or non-aromatic heterocycle forming between themortho- or ortho- and peri-fused systems; it being possible for thecarbon atoms of the said rings optionally to be substituted, in theirentirety or for only a portion of them, by R₀ radicals, R₀ having themeanings stated above for the substituents of the aromatic hydrocarbonradical of general formula (V′).

Mention may be made, as examples of R₁ to R₄ groups of heterocyclictype, of, inter alia, furyl, pyrrolyl, thienyl, isoxazolyl, furazanyl,isothiazolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyland pyranyl radicals and quinolyl, naphthyridinyl, benzopyranyl,benzofuranyl and indolyl radicals.

It is also possible that, among the R₁ to R₃ radicals, one of themrepresents a functional group and mention may in particular be made offunctional groups of NR₉R′₉ type in which R₉ and R′₉, which areidentical or different, represent a hydrogen atom, a linear or branchedalkyl group having from 1 to 12 carbon atoms, a phenyl group, a benzylgroup or an acyl group having from 2 to 12 carbon atoms, preferably anacetyl or benzoyl group.

Mention may be made, as more specific example, of, inter alia,2-methyl-2-butenoic acid.

A first class of substrates to which the process of the invention morepreferentially applies are substituted acrylic acids which areprecursors of amino acids and/or derivatives.

The term substituted acrylic acids is understood to mean all compoundswhere the formula derives from that of acrylic acid and where two atmost of the hydrogen atoms carried by the ethylenic carbon atoms aresubstituted by a hydrocarbon group or by a functional group.

They can be symbolized by the following chemical formula:

in the said formula (Va):

R₉ and R′₉, which are identical or different, represent a hydrogen atom,a linear or branched alkyl group having from 1 to 12 carbon atoms, aphenyl group or an acyl group having from 2 to 12 carbon atoms,preferably an acetyl or benzoyl group,

R₈ represents a hydrogen atom, an alkyl group having from 1 to 12 carbonatoms, a cycloalkyl radical having from 3 to 8 carbon atoms, anarylalkyl radical having from 6 to 12 carbon atoms, an aryl radicalhaving from 6 to 12 carbon atoms or a heterocyclic radical having from 4to 7 carbon atoms,

R₁₀ represents a hydrogen atom or a linear or branched alkyl grouphaving from 1 to 4 carbon atoms.

Mention may be made, as more specific examples of R₈ groups, of an alkylgroup, such as methyl, ethyl, isopropyl or isobutyl; a cycloalkyl group,such as cyclopentyl or cyclohexyl; an aromatic group, such as phenyl ornaphthyl, or a heterocyclic group, such as furyl, pyranyl, benzopyranyl,pyrrolyl, pyridyl or indolyl.

The R₁₀ group is preferentially a hydrogen atom.

Mention may be made, among substituted acrylic acids which areprecursors of amino acids, of N-acetyl-α-amino-β-phenylacrylic acid,N-benzoyl-α-amino-β-phenylacrylic acid, in which the phenyl ring isoptionally substituted by one or a number of alkyl, alkyloxy or hydroxylgroups, N-acetyl-α-amino-β-indolylacrylic acid,N-benzoyl-α-amino-β-indolylacrylic acid orN-acetyl-α-amino-β-isobutylacrylic acid.

Mention may more particularly be made of:

methyl α-acetamidocinnamate,

methyl acetamidoacrylate,

benzamidocinnamic acid,

α-acetamidocinnamic acid.

The invention also applies, entirely satisfactorily, to carrying out thehydrogenation of itaconic acid and/or derivative and more specificallyto the compounds corresponding to the formula (Vb):

in the said formula (Vb):

R₁₁ and R₁₂, which are identical or different, represent a hydrogenatom, a linear or branched alkyl group having from 1 to 12 carbon atoms,a cycloalkyl radical having from 3 to 8 carbon atoms, an arylalkylradical having from 6 to 12 carbon atoms, an aryl radical having from 6to 12 carbon atoms or a heterocyclic radical having from 4 to 7 carbonatoms,

R′₁₀ and R₁₀, which are identical or different, represent a hydrogenatom or a linear or branched alkyl group having from 1 to 4 carbonatoms.

The preferred substrates correspond to the formula (Vb) in which R₁₁ andR₁₂, which are identical or different, represent a hydrogen atom or analkyl group having from 1 to 4 carbon atoms and R₁₀ and R′₁₀, which areidentical or different, represent a hydrogen atom or a methyl group.

Mention may be made, as more specific examples, of in particularitaconic acid and dimethyl itaconate.

The process of the invention applies very particularly to thepreparation of arylpropionic acids by hydrogenation of a substratecorresponding to the formula (Vc):

in the said formula (Vc):

R₁₀ represents a hydrogen atom or a linear or branched alkyl grouphaving from 1 to 4 carbon atoms,

R₁₃ represents a phenyl or naphthyl group, optionally carrying asubstituent or a number of substituents R:

R can represent R₀, one of the following groups:

a linear or branched alkyl or alkenyl group having from 1 to 12 carbonatoms, preferably a linear or branched alkyl group having from 1 to 4carbon atoms,

a linear or branched alkoxy group having from 1 to 12 carbon atoms,preferably a linear or branched alkoxy group having from 1 to 4 carbonatoms,

a linear or branched acyloxy group having from 2 to 8 carbon atoms,preferably an acetoxy group,

a linear or branched acylamido group having from 1 to 8 carbon atoms,preferably an acetamido group,

an NO₂ group,

R can represent R₀′, one of the following, more complex groups:

a group of formula

 in which:

R₆ represents a valence bond; a saturated or unsaturated, linear orbranched, divalent hydrocarbon group having from 1 to 6 carbon atomssuch as, for example, methylene, ethylene, propylene, isopropylene orisopropylidene or one of the following groups known as Z:

—O—; —CO—; —COO—; —NR₇—; —CO—NR₇—; —S—; —SO₂— or —NR₇—CO—;

 in the said formulae R₇ represents a hydrogen atom or a linear orbranched alkyl group having from 1 to 6 carbon atoms,

R₀ has the meaning given above,

m is an integer from 0 to 4.

Mention may be made, as specific examples, of2-(3-benzoylphenyl)propionic acid (Ketoprofen®),2-(4-isobutylphenyl)propionic acid (Ibuprofen®) or2-(5-methoxynaphthyl)propionic acid (Naproxen®).

The selective asymmetric hydrogenation of the said substrates is carriedout by using, as catalysts, the metal complexes of the inventioncontaining the optically active diphosphine ligands of general formula(Ia) or (Ib).

When the diphosphine-transition metal complexes of the invention areused as catalysts for the asymmetric hydrogenation of unsaturatedcarboxylic acids, the desired product can be obtained with a highoptical yield.

By choosing one of the optical isomers of the diphosphine having a (+)or (−) optical rotation and by using a diphosphine-transition metalcomplex comprising the chosen isomer, the unsaturated carboxylic acid ishydrogenated to a compound having the desired absolute configurationwith a high optical yield.

The hydrogenation is generally carried out at a temperature of between20 and 100° C.

The hydrogen pressure can be between 0.1 and 200 bar and morepreferentially between 1 and 150 bar.

The diphosphine/transition metal complex is used so that the ratio ofthe number of atoms of metal present in the complex to the number ofmoles of the compound to be hydrogenated is between 0.1 and 0.0001.

The hydrogenation process is preferably implemented in an organicsolvent. Any solvent is used, in so far as it is stable under thereaction conditions.

A polar organic solvent is preferably used and more particularly thefollowing solvents:

aliphatic, cycloaliphatic or aromatic ethers and, more particularly,diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, methyltert-butyl ether, di-tert-butyl ether, ethylene glycol dimethyl ether orthe dimethyl ether of diethylene glycol; diphenyl ether, dibenzyl ether,anisole, phenetole, 1,4-dimethoxybenzene or veratrole; or 1,4-dioxane ortetrahydrofuran (THF),

mono- or polyhydroxylated alcohols and more particularly aliphaticmonoalcohols such as methanol, ethanol, propanol, butanol, sec-butanol,tert-butanol, pentanol or hexanol; aliphatic dialcohols such as ethyleneglycol, diethylene glycol or propylene glycol; or cycloaliphaticalcohols such as cyclopentanol or cyclohexanol,

aliphatic ketones such as acetone, methyl ethyl ketone or diethylketone,

aliphatic esters such as in particular methyl acetate, ethyl acetate orpropyl acetate.

The concentration of the substrate in the organic solvent advantageouslyvaries between 0.01 and 1 mol/l.

After the formation of the hydrogenation complex, a basic compound canoptionally be added.

This basic compound can be an alkali metal base, such as sodium orpotassium hydroxide, or else a primary, secondary or tertiary amine andmore particularly pyridine, piperidine or triethylamine and preferablytriethylamine.

The amount of base added is such that the ratio of the number of molesof base to the number of metal atoms present in thediphosphine/transition metal complex is between 0 and 25 and preferablybetween 0 and 12.

A preferential embodiment of the process of the invention is givenhereinbelow.

The said process is implemented in an autoclave which is purged using aninert gas, preferably nitrogen. Charging is preferably carried out ofthe substrate in solution in the organic solvent and then of thecatalyst, also in solution in the organic solvent.

The nitrogen is replaced by hydrogen.

The hydrogenation is completed when the hydrogen pressure becomesstable.

The hydrogenation process according to the invention allows access, withhigh enantiomeric excesses, to different enantiomers of manyderivatives.

The following examples, given without implied limitation, illustrate thepresent invention.

An implementational example of the present invention is givenhereinbelow by way of illustration, without any limiting nature.

Example 1 relates to the preparation of the new optically active(S,S)-(+)- and(R,R)-(−)-bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene]diphosphines.

In Examples 2 to 4, the synthesis of the catalysts used in hydrogenationis described.

Examples 5 to 13 correspond to the applicational examples.

EXAMPLES Example 1

Phospholyllithium: (III)

11.3 g (0.06 mol) of 1-phenyl-3,4-dimethylphosphole, 0.8 g of lithiummetal and 100 ml of distilled tetrahydrofuran are introduced into a 250ml round-bottomed flask.

The mixture is stirred under argon for 2 hours in a cold water bath.

The solution becomes brown.

The appearance of the phospholyllithium is monitored by ³¹P NMR.

³¹P NMR=δ(THF)=55.8 ppm.

In order to trap the phenyllithium, 2.7 g of aluminium chloride areadded at 0° C.

The mixture is allowed to react for 30 minutes at 0° C.

1,1′-Bisphosphole: (IV)

6 g (0.025 mol) of diiodine, in solution in 25 ml of tetrahydrofuran,are added dropwise at ambient temperature to the above mixture.

When 90% of this solution is introduced, the disappearance of (III) isconfirmed by ³¹P NMR.

³¹P NMR=δ(THF)=−22.4 ppm.

The 1,1′-bisphosphole (IV) is extracted under nitrogen from the mixtureusing hexane.

Bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene]: (I m) and (I r)

The above solution is evaporated to dryness, with air excluded andbrought to 140° C.

8 g of diphenylacetylene are then introduced and the reaction mixture isallowed to react for 15 to 20 minutes.

The disappearance of (IV) is again monitored by ³¹P NMR.

The spectrum is composed of 2 singlets corresponding to the twodiastereoisomers.

The product is extracted with ether and washed with water.

The organic phases are combined and then evaporated to dryness.

The residue is then purified by chromatography on a silica column(elution with hexane to remove the excess diphenylacetylene and thenwith a hexane/dichloromethane: 80/20 by volume mixture).

The overall yield is 30%.

Complex of Palladium(II) with (I m) and (I r): (VI m) and (VI r)

5 g (8.25 mmol) of (I m) and of (I r) are introduced into a 500 mlround-bottomed flask and are dissolved in 200 ml of dichloromethane.

3 g (8.25 mmol) of PdCl₂(PhCN)₂ in 100 ml of dichloromethane are thenadded dropwise.

The reaction, carried out under argon, is immediate.

The solution is evaporated to dryness and the residue is subjected tochromatography on silica in order to separate the two diastereoisomers.

Elution is carried out using dichloromethane in order to remove theimpurities, then with a mixture of dichloromethane and ethyl acetate:95/5 by volume in order to separate the racemate and finally with adichloromethane/ethyl acetate: 80/20 by volume mixture in order toseparate the meso.

³¹P NMR=δ(CH₂Cl₂)=81.9 ppm—minor isomer corresponding to the racemate.

³¹P NMR=δ(CH₂Cl₂)=88.1 ppm—major isomer corresponding to the meso.

Decomplexation of (VI r)

1.5 g (0.002 mol) of racemic (VI r) and 20 ml of dichloromethane areintroduced into a 100 ml round-bottomed flask.

0.5 g of sodium cyanide and a few milliliters of water (3 ml) are thenadded.

The mixture is stirred vigorously under argon for 10 to 15 minutes.

The bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] (I r) is thenextracted with dichloromethane.

The organic phase is washed with water and then dried over sodiumsulphate.

Pure (I r) is thus recovered.

The overall yield of the separation of the diastereoisomers is 90%.

The characterization of the racemic mixture (I r) is as follows:

³¹P NMR=δ(CDCl₃)=−13.2 ppm.

¹H NMR=δ(CDCl₃)=1.31 (s, 6H, CH₃), 1.69 (s, 6H, CH₃), 2.02-2.20 (m, 4H,CH₂ bridge), 6.86-7.29 (m, 20H, phenyl protons).

Binuclear Palladium(II) Complex:

290 mg (0.5 mmol) of racemic (I r) and 300 mg (0.5 mmol) of(+)-di-μ-chlorobis{2-[1-(dimethyl-amino)ethyl]phenyl-C,N}dipalladium areintroduced under nitrogen into 12 ml of benzene.

Complexation is rapid and monitored by ³¹P NMR.

The brown solution is evaporated to dryness and the residuechromatographed in order to separate the two diastereoisomers(toluene/ethyl acetate:80/20 by volume elution).

The two pure isolated enantiomers are thus recovered in the form of twodiastereoisomer complexes of formula:

These enantiomers are recovered pure by decomplexing as for (VI r).

The diphosphines of formulae (Ia) and (Ib) respectively are identifiedas follows:

³¹P NMR=δ(CDCl₃)=−13.2 ppm; [α]_(D)=+231° (c=1, C₆D₆).

³¹P NMR=δ(CDCl₃)=−13.2 ppm; [α]_(D)=−198° (c=1, C₆D₆)

(with an [α]_(D) determined for a concentration of 10 mg/ml and atambient temperature).

Example 2

In this example, the preparation of a complex of formula[Rh⁺(COD)(P*P)]PF₆ ⁻, in which COD represents 1,5-cyclooctadiene and(P*P) represents the diphosphine of formula (Ib), is described.

11.6 mg of Rh(COD)₂PF₆ are dissolved, under argon, in 3 ml of acetone ina 10 ml Schlenk flask.

A solution of 7.5 mg of the said diphosphine in acetone is then addeddropwise, still under an inert gas.

After stirring for a few minutes, the expected complex is obtained.

³¹P NMR: δ=73.8 ppm, J(Rh-P)=155 Hz.

Example 3

In this example, the preparation of a complex of formula[Rh⁺(COD)(P*P)]PF₆ ⁻, in which COD represents 1,5-cyclooctadiene and(P*P) represents the diphosphine of formula (Ia), is described.

The said complex is prepared according to the same procedure as that ofExample 2.

Example 4

In this example, the preparation of a complex of formula RuBr₂(P*P), inwhich (P*P) represents the diphosphine of formula (Ia), is described.

7.5 mg of diphosphine and 4 mg of Ru(COD)(allyl)₂ are dissolved, underargon, in 2 ml of acetone in a 10 ml Schlenk flask.

0.11 ml of a 0.29M aqueous hydrobromic acid solution in methanol is thenadded dropwise.

Stirring is carried out for 30 min at ambient temperature (˜20° C.) andthe expected complex is obtained.

³¹P NMR: AB system, δ=98.2 ppm, 88.1 ppm (J_(AB)=21 Hz).

Example 5

In this example, the asymmetric hydrogenation is carried out, using thecatalyst of Example 2, of the following compound:

400 mg of the said compound are dissolved in 20 ml of methanol in around-bottomed flask.

The complex 1 of Example 2 is then prepared as proposed above.

The acetone is evaporated and the residue is dissolved in 5 ml ofmethanol.

The 2 solutions are then introduced into an autoclave which has beenpurged beforehand and maintained under a nitrogen atmosphere.

Hydrogen is then introduced to a pressure of 3 atmospheres.

Agitation is carried out at 20° C. for 1 h.

The excess hydrogen is discharged and the reaction solution isrecovered.

The solvent is evaporated and the residue analysed by ¹H NMR in order toconfirm the progress of the reaction.

The reaction is quantitative.

The enantiomeric excess is determined by chiral high performance liquidchromatography (Shandon®, 150×6.4 mm, HSA protein chiral column) and theabsolute configuration of the product by measurement of the [α]_(D) andby polarimetry.

With the diphosphine (Ib), ee≧98%, [α]_(D) (ethanol, c=1)>0.

Example 6

In this example, the asymmetric hydrogenation is carried out, using thecatalyst of Example 4, of the following compound:

The implementation is the same as with 1. The difference lies in thecatalyst, the reaction time is less than 24 hours and the pressureatmospheric.

With the diphosphine (Ia), ee=80%, [α]_(D) (ethanol, c=1)<0.

Example 7

In this example, the asymmetric hydrogenation is carried out, using thecatalyst of Example 3, of the following compound:

The implementation is identical.

165 mg of itaconic acid are introduced, still with the same amount ofsolvent and of catalyst.

The reaction is carried out at ambient temperature, in less than 3hours.

With the diphosphine (Ia), ee=80%, [α]_(D) (ethanol, c=2.16)<0.

Example 8

In this example, the asymmetric hydrogenation is carried out, using thecatalyst of Example 2, of the following compound:

245 mg of the said compound are dissolved in 8 ml of methanol in aflask.

The complex 1 of Example 2 is then prepared as proposed above.

The acetone is evaporated and the residue is dissolved in 2 ml ofmethanol.

This solution is then introduced into the flask, which is itself placedin the autoclave which has been purged beforehand and maintained underan argon atmosphere.

Hydrogen is then introduced to a pressure of 4 atmospheres.

Agitation is carried out at 20° C. for 2 hours.

The excess hydrogen is discharged and the reaction solution isrecovered.

The reaction solution is evaporated and the residue analysed by ¹H NMRin order to confirm the progress of the reaction.

The progress is 30%.

The enantiomeric excess (ee) is determined by chiral high performanceliquid chromatography (Chiral pack-AD column).

With the diphosphine (Ib), ee>98%.

Example 9

In this example, the preparation of a complex of formula Ru(OAc)₂(P*P),in which OAc represents an acetate group and (P*P) the diphosphine offormula (Ib), is described.

10 mg of diphosphine (Ib) and 6 mg of Ru(Me-allyl)₂(COD) are dissolved,under argon, in 2 ml of acetone in a 10 ml Schlenk flask.

A solution of 4 mg of CCl₃CO₂H in 1 ml of methanol is then addeddropwise.

After stirring for a few minutes, a large excess of sodium acetate,dissolved in 1 ml of methanol, is added and the expected complex isobtained after stirring for a few minutes.

³¹P NMR: δ=107.9 ppm

Example 10

In this example, the preparation of a complex of formula Ru(OAc)₂(P*P),in which OAc represents an acetate group and (P*P) the diphosphine offormula (Ia), is described.

The said complex is prepared according to the procedure of Example 9.

Example 11

In this example, the asymmetric hydrogenation is carried out, using thecatalyst of Example 9, of the following compound:

The implementation is the same as in Example 8. The difference lies inthe catalyst, the reaction time, which is 12 hours, and the pressure of130 atmospheres. The progress is 12%.

With the diphosphine (Ib), ee>95%.

Example 12

In this example, the asymmetric hydrogenation is carried out, using thecatalyst of Example 10, of the following compound:

100 mg of the said compound are dissolved in 4 ml of methanol in around-bottomed flask.

The complex of Example 9 is then prepared as proposed above.

The two solutions are then introduced into an autoclave which has beenpurged beforehand and maintained under a nitrogen atmosphere.

Hydrogen is then introduced to a pressure of 4 atmospheres.

Agitation is carried out at 20° C. for 3 hours.

The excess hydrogen is discharged and the reaction solution isrecovered.

The solution is evaporated and the residue analysed by ¹H NMR in orderto confirm the progress of the reaction.

The progress is 90%.

The enantiomeric excess (ee) is determined by chiral high performanceliquid chromatography (Chiral cell -OJ-R column).

With the diphosphine (Ia), ee=57%.

Example 13

In this example, the asymmetric hydrogenation is carried out, using thecatalyst of Example 2, of the following compound:

270 mg of the said compound are dissolved in 8 ml of methanol in aflask.

The complex 1 of Example 2 is then prepared as proposed above.

The acetone is evaporated and the residue is dissolved in 3 ml ofmethanol.

This solution is then introduced into the flask, which is itself placedin the autoclave which has been purged beforehand and maintained underan argon atmosphere.

Hydrogen is then introduced to a pressure of 5 atmospheres.

Agitation is carried out at 20° C. for 2 hours.

The excess hydrogen is discharged and the reaction solution isrecovered.

The reaction solution is evaporated and the residue analysed by ¹H NMRin order to confirm the progress of the reaction.

The progress is 70%.

The enantiomeric excess (ee) is determined by chiral high performanceliquid chromatography (Chiral cell -OJ-R column).

With the diphosphine (Ib), ee>98%.

What is claimed is:
 1. A method for the asymmetric hydrogenation of asubstrate, which comprises contacting the substrate with hydrogen and acomplex comprising an optically active diphosphine and a transitionmetal wherein the ligand corresponds to one of the following formulae:


2. Method according to claim 1, wherein the transition metal is chosenfrom: rhodium, ruthenium, rhenium, iridium, cobalt, nickel, platinum orpalladium.
 3. Method according to claim 2, wherein said complex isrepresented by the following formulae: [M L₂(P*P)]Y  (IIa) [ML₂(P*P)]Y  (IIb) in said formulae: (P*P) represents, in the formula(IIa), the diphosphine of formula (Ia) and, in the formula (IIb), thediphosphine of formula (Ib), M represents rhodium or iridium, Yrepresents an anionic coordinating ligand, and L represents a neutralligand.
 4. Method according to claim 3, said complex corresponding tothe formula (IIa) or (IIb) in which: L represents an olefin having from2 to 12 carbon atoms and two L ligands can be joined to one another inorder to form a linear or cyclic polyunsaturated hydrocarbon chain; andY represents PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻, BPh₄ ⁻, ClO₄⁻, CN⁻ or CF₃SO₃ ⁻, halogen anion, a 1,3-diketonate, alkylcarboxylate orhaloalkylcarboxylate anion substituted with a lower alkyl radical, or aphenylcarboxylate or phenoxide anion in which the benzene ring can besubstituted by lower alkyl radicals and/or halogen atoms.
 5. Methodaccording to claim 3, said complex comprising an optically activediphosphine and iridium represented by the following formulae: [IrL(P*P)]Y  (IIIa) [IrL (P*P)]Y  (IIIb) in said formulae (P*P), L and Yhave the meanings given for formulae (IIa) and (IIb).
 6. Methodaccording to claim 1, said complex comprising an optically activediphoshine and ruthenium represented by the following formulae: [RuY₁Y₂(P*P)]  (IVa) [RuY₁Y₂ (P*P)]  (IVb) in said formulae: (P*P) represents,in the formula (IVa), the diphosphine of formula (Ia) and, in theformula (IVb), the diphosphine of formula (Ib), and Y₁ and Y₂, which areidentical or different, represent a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆⁻, BPh₄ ⁻, ClO₄ ⁻ or CFSO₃ ⁻, halogen anion or a carboxylate anion. 7.Method according to claim 1, said complex comprising an optically activediphosphine and ruthenium represented by the following formulae:[RuY₁Ar(P*P)Y₂]  (IVc) [RuY₁Ar(P*P)Y₂]  (IVd) in said formulae: (P*P)represents, in the formula (IVc), the diphosphine of formula (Ia) and,in the formula (IVd), the diphosphine of formula (Ib), Ar representsbenzene, p-methylisopropylbenzene or hexamethylbenzene, Y₁ represents ahalogen anion, and Y₂ represents an anion.
 8. Method according to claim1, wherein the hydrogenation is conducted at a temperature within therange of 20° to 100° C.
 9. Method according to claim 1, wherein thehydrogen pressure is within the range of 0.1 to 200 bar.
 10. Methodaccording to claim 1, wherein the ratio of the number of atoms of metalin the complex to the number of moles of the substrate to behydrogenated is from 0.1 to 0.0001.